The FDA has approved talazoparib (Talzenna) in combination with enzalutamide (Xtandi) for adults with metastatic hormone-sensitive prostate cancer carrying homologous recombination repair (HRR) gene mutations. The decision covers patients who are androgen pathway modulation–naïve or -sensitive (mAPMN/S), with eligibility based on tumor tissue or circulating tumor DNA next-generation sequencing. The approval was based on results from the randomized, double-blind, placebo-controlled TALAPRO-3 trial, which enrolled 599 patients. Participants received continuous androgen deprivation therapy, then were randomized 1:1 to talazoparib plus enzalutamide or placebo plus enzalutamide. Investigator-assessed radiographic progression-free survival (rPFS) was the primary endpoint. Median rPFS was not reached in the talazoparib arm versus 45.8 months in the placebo arm (hazard ratio 0.48; p<.0001). Overall survival data were immature at the time of the rPFS analysis, according to the report. Clinically, the label expands PARP inhibitor use into the metastatic hormone-sensitive setting for a genetically defined population, with prespecified HRR categories including BRCA1, BRCA2, ATM, ATR, PALB2, and others.